1. Field of the Invention.
The present invention relates to the use biocidal compositions of matter to eliminate infections from various body cavities. More particularly, the present invention concerns the use of biocidal compositions for eliminating infections in the thoracic cavity, abdominal cavity, synovial spaces, urinary bladder, lungs, sinus cavities, external auditory canal, oral pharynx, pericardial space, and the like by microorganisms and viruses. Even more particularly, the present invention concerns the elimination of infections including pathogenic microorganisms including Gram negative and positive bacteria, yeast, fungi, rickettsia and the like as well as normally nonpathogenic microorganisms present in the body cavities or spaces, which spaces or cavities do not normally harbor or support the growth of such organisms.
2. Prior Art
It is recognized and well documented that microorganisms present in the internal spaces and tissues of the body can cause disease i.e. infection, leading to physical debility of the animal or person and may even cause death. Today, typically, microorganism infection is normally treated with antibiotics. Antibiotics are made from compounds that interfere with the normal growth and proliferation of microorganisms. The action of these antibiotics involves specific interference with cell wall synthesis, protein synthesis or the like in the bacteria as they attempt to proliferate. There are analogous compounds prescribed for the treatment of fungal and yeast infections. There are a limited number of medications that interfere with the proliferation or viruses and viral particles in host cells preventing disease or discomfort normally caused by the virus.
Antibiotics normally act by interfering with biochemical mechanisms internal to the microorganism. Antibiotics are used as topical creams but are primarily administered either orally or in injectable form. The antibiotic then circulates through the blood stream and permeates the infected tissue where it comes in contact with the infecting organisms.
It is widely recognized by medical practitioners that the use of antibiotics has several problems and limitations that can lead to unwanted side effects or ineffective action against the infecting organisms. It is also recognized that any one antibiotic is effective against a limited spectrum of microorganisms and that this limited action frequently requires the medical practitioner to evaluate the effectiveness of the antibiotic in vitro prior to use which test is referred to in medical practice as a culture and sensitivity assay. The use of an antibiotic that is not active against the specific microorganism involved in the infection will not eliminate the infection and can actually accelerate growth of the organism by eliminating competing organisms leading to further progress of the resulting disease.
On the other hand testing for effectiveness of an antibiotic can delay treatment and result in further progress of the infection which can lead to severe consequences including death and hence the medical practitioner will usually take samples of the infecting microorganism for testing and start the patient on a broad spectrum antibiotic while waiting for the test results. The use of an antibiotic that is not effective against the infecting organism, however, can actually cause an increase in the growth of the infecting organism as stated.
Further, complications from the use of antibiotics can result from microorganisms developing resistance to the antibiotic. Microorganisms can develop resistance to antibiotics by exposure to subinhibitory levels of the antibiotic which subinhibitory levels allows the growth of any bacteria present that have only marginal susceptibility. Once the resistant strains proliferate, they become the dominant organism causing infection. Though not as common, strains of bacteria have been know to develop resistance to antimicrobial compositions of matter used for sanitizing and disinfecting inanimate surfaces and objects. The overuse and incorrect use of antibiotics in recent years has led to the emergence of bacteria that are resistant to all known antibiotics and present a severe health threat throughout the world. These organisms include but are not limited to antibiotic resistant tuberculosis, methicillin resistant Staphylococcus aureus and vancomycin resistant enterococci. While new antibiotics are continuously developed to deal with this problem it is recognized that the use of compounds such as those found in antibiotic compositions that interfere with normal biochemical mechanisms of growth and proliferation of microorganisms is likely to ultimately lead to the development of strains of bacteria resistant to the new compounds as well.
Hence, there is a serious and pressing need for the development of medications and methods of treatment of infections by bacteria, yeast, mold, rickettsia, viruses and the like that do not have the limitations and side effects observed with antibiotics.
Compositions of matter that kill microorganisms by direct action on the cell wall, referred to as cell lysis, are broadly known and are referred to as biocidal agents. These agents are used to eliminate microorganisms from various surfaces and materials including the surface of the body. Biocidal agents are not capable of circulating through the blood stream and permeating tissues and hence must be applied directly to the offending microorganisms.
Those skilled in the art recognize many biocidal compositions which employ a variety of substances as the active agent including, for example, quaternary ammonium compounds, halogens, fatty acids, anionic surfactants, organic acids, and sulfated and sulfonated aliphatic acids. For example, U.S. Pat. No. 5,143,720 to Lopes discloses mixtures of anionic surfactants and organic acids for use as mouthwash and as bactericides for food and food processing equipment. U.S. Pat. No. 4,404,040 to Wang discloses sanitizing concentrate compositions comprising an aliphatic short chain fatty acid, a hydrotrope or solubilizer for the fatty acid and an acid to produce a pH between 2 and 5 when diluted with water for use in food processing systems. U.S. Pat. No. 4,715,980 to Lopes, et al. discloses sanitizing compositions comprising a dicarboxylic acid and an acidic component that produces a pH below about 5 when diluted with water. U.S. Pat. No. 3,867,300 to Karabinos, et al. discloses bactericidal compositions containing a monocarboxylic fatty acid is protonated making the acid hydrophobic.
While the protonated and hence hydrophobic form of fatty acids is far more biocidal than the unprotonated, hydrophilic form, the hydrophobic form is insoluble in water. The use of a hydrotrope to solubilize the hydrophobic form of fatty acids allows them to remain in solution at a pH below 5.0. It is the use of the protonated form of fatty acids in the presence of suitable hydrotropes that allows complete elimination of microorganisms from internal body spaces or organs in animals and man, which elimination results in the cure or arrest of the associated disease state.
However, as is known to those skilled in the art to which the present invention pertains, the internal organs and spaces of the body of man or animals ordinarily secrete fluids rich in protein and inorganic ions that act to maintain the pH of that tissue or space between about 7.0 to about 7.8. The only tissue or space in the animal body that has a pH below 5.0 is the stomach. The contents of the stomach are emptied into the small intestine and in the first few centimeters of the small intestine secretion from the pancreas acts to raise the pH to 6.5 or above.
There are further complicating aspects of biology that limit the use of biocidal compositions in the internal spaces and organs. The proteins, glycoproteins, lipoproteins, lipids and phospholipids and the like that are secreted from many tissues will act to nourish and harbor microorganisms from direct attack by biocidal compositions of matter. It is a critical aspect of antibiotics that they are able to penetrate most tissues and secretions of the body and hence enter the cell body of the offending microorganism to stop growth of that organism.
Hence the use of fatty acid-based biocidal compositions in the spaces and organs of the body of man and animals to eliminate disease caused by microorganisms will have very limited efficacy unless the pH of the composition is maintained below about 5.0 and, preferably, below about 4.5 by the inclusion of an appropriate organic acid and unless a suitable surfactant is used to expose the microorganism to the biocidal action of the fatty acid.
It has long been recognized that biocidal compositions of matter employing fatty acids can be used to kill microorganisms on the outside of the body and on inanimate surfaces. It is nowhere mentioned in the art, however, nor has it been recognized nor is it readily apparent that these compositions of matter can be used in the internal spaces and organs of the body of man and animals at pH above about 5.0 to treat disease by the elimination of microorganisms.
Fatty acid based biocides are known in the art to be employed in the treatment of Helicrobacter pylori infections of the stomach. See, inter alia, Wider U.S. Pat. No. 6,071,761, the disclosure of which is hereby incorporated by reference. The stomach as described above, however, has a pH below 5.0 and the lining of the stomach is known to be able to tolerate low pH conditions without any damage or pathologic changes. Hence it is not readily apparent from this use nor is it suggested in any prior art that acidic compositions of matter employing fatty acids held in solution by appropriate hydrotropes can be tolerated or used in other areas of the body of man or animals. It is to this to which the present invention is directed.
The composition of the present invention meets the need for elimination of pathogenic organisms from the internal spaces or organs of animals and humans by direct contact with bactericidal and fungicidal agents, avoiding the use of antibiotics. Use of low levels of organic acid in the composition allows the fatty acid(s) to remain protonated but does not cause damage to the body tissues.
In accordance with the present invention there is provided a biocidal or antimicrobial composition, based on USP or food grade components for the treatment of microbial infections of the body spaces and organs of man or animals normally that normally have a pH of 5.0 and above, comprising:
(a) an antimicrobial active agent,
(b) a hydrotrope or solubilizer, and
(c) a hydrotrope compatible acid.
The composition may be in concentrate or a use solution. As a use solution, the concentrate is admixed with deionized, pyrogen-free water and may be rendered isotonic to body fluids by the addition of the appropriate amount of sodium chloride (NaCl).
The use composition hereof has a pH ranging from about 1.0 to about 5.0 and, preferably ranges from about pH 2.5 to about pH 4.0.
The composition hereof is administered as a liquid either orally or through a suitable delivery system, such as a catheter, an enema tube, needle or the like. Similarly, the composition may be administered as a solid in tablet or encapsulated form.
For a more complete understanding of the present invention, reference is made to the following detailed description and accompanying examples.